The proposed research is an attempt to characterize the transport pathways for water and solutes across the epithelium of proximal renal tubules. Electrophysiological techniques will be used in order to assess the permeability properties of the intercellular and the cellular pathways crossing the tubular wall. An attempt will be made to separate the different transport routes and to determine the transport coefficients of the parallel and series barriers of the epithelium. In addition the physiological role of intercellular spaces in the control of net salt and water movement will be explored. The electrogenesis of the transepithelial potential difference and of the cell membrane potential differences will be further investigated. The coupling beween salt and water transport and the movement of other solutes will be assessed. In parallel, the morphological correlates of the intraepithelial routes followed by salt and water movement will be studied by means of electron microscopy. Finally, the knowledge and understanding of the various parameters of the proximal tubular epithelium will allow the integration of such information with models that can account for the phenomenon of isotonic water reabsorption and for the overall electrical behavior of the renal tubule.